PubMed Health⌕ Search

Biomedical subjects

C Mahony

Publications and source records attributed to C Mahony.

At least 19 recordsLinked to original sources
PubMed1995

A role for FGF-8 in the initiation and maintenance of vertebrate limb bud outgrowth.

BACKGROUND: The outgrowth of the vertebrate limb bud is the result of a reciprocal interaction between the mesenchyme and a specialized region of the ectoderm, the apical ectodermal ridge (AER), which overlies it. Signals emanating from the AER act to maintain the underlying mesenchyme, called the progress zone, in a highly proliferative and undifferentiated state. Removal of the AER results in the cessation of limb bud growth, thus causing limb truncation. The best candidates for this AER-derived signal are members of the fibroblast growth factor (FGF) family, in particular FGF-4, which can maintain limb bud outgrowth following removal of the AER. However, FGF-4 is only expressed after considerable outgrowth has occurred and a well-developed limb bud has formed, and then only in the posterior part of the AER. Likewise, the other FGFs studied to date are not candidates for this activity. RESULTS: We report evidence that a recently identified member of this family, FGF-8, is expressed in the ectoderm of the prospective limb territory prior to morphological outgrowth of the limb bud in both mouse and chick. Thereafter, expression is maintained throughout the AER during limb development. We have produced and purified the FGF-8 protein, and shown that it will substitute for the AER in maintaining limb bud outgrowth in mouse embryos from which the AER has been surgically removed. FGF-8 does not, however, maintain expression of the sonic hedgehog gene. CONCLUSIONS: These results indicate that FGF-8 is an AER-derived mitogen that stimulates limb bud outgrowth. Moreover, our data suggest that FGF-8 may also be an ectodermally derived mitogen that stimulates the onset of limb bud outgrowth (budding) in the absence of a morphological AER, and indicate the possible involvement of FGF-8 in the establishment of the limb field.

Amino Acid Sequence↗
PubMed1995

Effect of aspirin on spontaneous contrast in the brachial veins of normal subjects.

Blood cell aggregates are thought to be the cause of spontaneous echo contrast (SEC), although there is disagreement as to whether red cell or platelet aggregates produce this effect. One way to differentiate between these 2 possibilities is to evaluate the effect of aspirin on SEC because aspirin would not be expected to affect red cell aggregates. To eliminate the need to perform repetitive transesophageal echocardiographic studies, and the possible effect of the underlying disease process on SEC, the effect of aspirin on SEC in the brachial vein was studied in normal volunteers using a single-blind, before-and-after study design. Other factors known to affect blood echogenicity including hematocrit, sedimentation rate, and the presence of platelet aggregates by microscopy were also studied. The amount of SEC was quantitated by image analysis and expressed as the aggregate score. The results in 10 volunteers showed that all had SEC in brachial veins before aspirin, but there was no significant day-to-day variation in the amount of SEC during the control period (mean +/- SEM 104,248 +/- 23,088, 153,722 +/- 35,664, and 124,568 +/- 22,827 for days 1, 3, and 5, respectively). A significant decrease in the aggregate score occurred after 7 days of aspirin, 650 mg twice a day (51,690 vs 127,513, p = 0.002); this was accompanied by a striking decrement in the size of the largest platelet aggregate found in venous blood. Aspirin caused no significant change in the hematocrit or sedimentation rate. These results indicate that there is a component of SEC that is aspirin-sensitive and is likely to represent platelet aggregates.

Adult↗
PubMed1994

Intravascular platelet aggregation and spontaneous contrast.

The purpose of this study was to determine why spontaneous contrast developed after general anesthesia in dogs. Twenty-seven dogs underwent echocardiography before and after pentobarbital or chloralose-urethane general anesthesia. The results showed that none of the 12 dogs receiving pentobarbital and 10 of 15 dogs receiving chloralose-urethane anesthesia developed contrast, in association with large platelet and platelet-neutrophil aggregates (P < 0.01); this effect could also be reproduced in vitro. The administration of adenosine diphosphate or antiplatelet antibody to nine dogs confirmed that intravascular platelet aggregation can cause ultrasonic contrast. The implications of these findings for patients with spontaneous contrast are discussed.

Anesthesia, General↗
PubMed1992

The effect of heparin versus citrate on blood echogenicity in vitro: the role of platelet and platelet-neutrophil aggregates.

There is no consensus among investigators regarding which anticoagulant to use when studying the causes of in vitro blood echogenicity, despite the fact that heparin and calcium-chelating anticoagulants may have disparate effects due to their differing effects on platelets. This study quantitated the echogenicity of heparinized blood compared to citrated blood and found that it was greater in heparinized blood than in citrated blood when paired samples from the same donor, drawn at the same time were compared. By microscopic examination of the blood, this difference appeared to be due to the formation of platelet and platelet-neutrophil aggregates in the heparinized blood. This hypothesis was tested by comparing the echogenicity of heparinized blood to that of heparinized blood following platelet and white cell depletion. The results showed that taking away platelets and white cells virtually eliminated the echogenicity of heparinized blood; the impact of this result is discussed in the context of in vivo spontaneous contrast.

Animals↗
PubMed1992

Red cell aggregation and the echogenicity of whole blood.

To study the relationship between red cell aggregation and whole blood echogenicity, red cell aggregation was quantitated by a photometric method, whole blood echogenicity was quantitated by videodensitometry and sedimentation rate was quantitated by a modified Westergren method. Changes in red cell aggregation were produced by alterations in the hematocrit. The results showed that red cell aggregation increased in a linear fashion with increases in hematocrit. The sedimentation rate decreased in a linear manner with increases in hematocrit. Whole blood echogenicity showed a biphasic response, with an initial increase in echogenicity, peaking at hematocrits varying from 14-24% and decreasing thereafter. Over the physiologic range of hematocrits, an increase in the formation of red cell aggregates is associated with a decrease in the echogenicity of whole blood. Thus, red cell aggregates were not visible using our ultrasound equipment at physiologic hematocrits, and the echo contrast in blood under our experimental conditions at these hematocrits must represent either plasma spaces, platelet aggregates or possibly white cell aggregates. The association between spontaneous contrast and a propensity for thromboembolism imply that platelet aggregates are the most likely origin of in vivo echo contrast in flowing blood.

Animals↗
PubMed1992

Spontaneous echocardiographic contrast in the thoroughbred: high prevalence in racehorses and a characteristic abnormality in bleeders.

Spontaneous echocardiographic contrast is the term used by ultrasonographers to describe particulate material visible in intracardiac blood by ultrasound. The purpose of the present study was to determine the prevalence of spontaneous contrast in a farm population of Thoroughbreds and in the farm's racehorses. The results showed that spontaneous echocardiographic contrast is common in Thoroughbreds, and that the prevalence of contrast is affected by age, male gender, racing and pregnancy. The amount of right-sided cardiac contrast was quantitated by videodensitometry and was increased in horses with a history of exercise-induced pulmonary haemorrhage, in comparison with racehorses without a history of bleeding. Since circulating platelet aggregates are known to produce pulmonary haemorrhage in experimental animals and their presence has been associated with echocardiographic contrast, additional studies evaluating platelet aggregates as the aetiologic agent for exercise-induced pulmonary haemorrhage are warranted.

Age Factors↗
PubMed1992

Development of spontaneous echocardiographic contrast after surgical trauma.

To determine if hypercoagulability is associated with contrast, surgical trauma was studied in a canine model. Contrast increased in the right heart and aorta after laparotomy, but not after anesthesia alone in either the right or the left heart. The inferior vena cava had the largest amount of contrast after surgery, implying that contrast development was primarily a local response to injury. The cellular composition of this contrast was not determined, but it occurred in the absence of changes in systemic rheologic or hematologic parameters and was not affected by heparin administration.

Anesthesia, Intravenous↗
PubMed1989

A computerized analysis of platelet aggregation detected by ultrasound.

The purpose of this study was to determine if computerized image processing could be used to characterize platelet aggregation visualized by ultrasound. Citrated whole blood (WB) or platelet-rich plasma (PRP) was imaged with a 12 mHz transducer before and after the addition of adenosine diphosphate. The images were digitized using a 512 x 512 pixel resolution with 256 levels of gray. Raster interference was eliminated by filtering and aggregates were separated from background by gray level discrimination. The results showed that platelet aggregation in PRP can be described by the number of aggregates counted, their sizes or their gray levels. However, aggregation in WB can be detected only by the sizes or gray levels of the aggregates due to the greater echogenicity of ex vivo WB. This methodology, applied to ultrasonic images of brachial arteries and veins, demonstrates that venous particles are common in patients and normal controls, but arterial particles are more common in patients. Differences in the size and brightness of these particles may have prognostic implications.

Arm↗
PubMed1987

The ultrasonic detection of platelet aggregates.

The echogenicity of platelet aggregates in platelet-rich plasma and whole blood was evaluated in stirring and flowing in vitro models. Real-time two dimensional ultrasonic images were obtained with transducers operating at 3.0, 5.0, 10 and 12 mHz. Platelet-rich plasma was not echogenic. The addition of adenosine diphosphate (ADP) resulted in the formation of multiple, discrete echoes that increased in size and intensity. This echogenicity was time and dose-dependent and could be quantitated by videodensitometry. Whole blood was echogenic, but the addition of ADP resulted in a time and dose-dependent increase in the size and echogenicity of the reflections. The overall echogenicity of whole blood declined with the development of platelet aggregates. There is inter- and intra-aggregate variability in the echogenicity of aggregates. Aggregates were best seen with transducers operating at the higher frequencies. These results imply that the detection of in vivo platelet aggregates may be feasible with ultrasonic imaging.

Adenosine Diphosphate↗
PubMed1984

In vitro stability of sodium nitroprusside solutions for intravenous administration.

A sensitive high-performance liquid chromatographic assay for nitroprusside using an ion-exchange column and UV detection was developed to evaluate the stability of aqueous solutions of sodium nitroprusside in light-protected glass and plastic containers and during simulated infusions. The results showed that sodium nitroprusside is stable in 5% dextrose, normal saline, and lactated Ringer's solutions in light-protected glass or plastic containers. In addition, there was no decrease in the delivered potency of sodium nitroprusside solutions during simulated infusions lasting up to 24 h.

Chromatography, High Pressure Liquid↗
PubMed1983

Clinical pharmacokinetics of dipyridamole.

The pharmacokinetics off dipyridamole were studied in six normal subjects and 20 patients. The normal subjects received 20 mg IV each and five also took a 50 mg oral dose. Concentrations after the intravenous dose showed a tri-exponential decline with a terminal half-life of 11.6 +/- 2.2 hr (mean +/- S.D.). Total plasma clearance was 138 +/- 30 ml/min and the apparent volume of distribution was 141 +/- 51 l. Peak concentrations after oral dipyridamole occurred 2--2.5 hr after the dose. Systemic availability of the oral dose was 52 +/- 23%. Plasma protein binding was 99.13 +/- 0.24%. Twenty patients, admitted for coronary artery bypass grafting, received total daily doses of 150 mg, either as 50 mg tid or 75 mg bid. Based on drug cumulation during chronic dosing, the terminal half-life averaged about half a day. There was wide interpatient variability, averaging about 10-fold, in observed plasma concentrations for both dosage regimens. The bid regimen was not associated with lower trough concentrations of the drug than the tid regimen. These results indicate that dipyridamole concentrations vary widely in patients receiving the drug, and suggest that it could be administered twice a day, and that dipyridamole levels should be monitored for the antithrombotic effect in clinical studies.

Administration, Oral↗
PubMed1983

Kinetics and metabolism of sulfinpyrazone.

Six normal subjects (three men and three women) took 200 mg sulfinpyrazone in two oral preparations, a capsule and a suspension. Plasma and urine levels of sulfinpyrazone and the sulfide, p-hydroxy, and sulfone metabolites were measured over three days. The plasma sulfinpyrazone/time concentration profiles indicated a postabsorptive biexponential decline with a mean terminal half life (t1/2) of 299 +/- 107 min. There was intersubject variation in the formation of the metabolites, the greatest being with the sulfide metabolite. Mean t1/2 of the sulfide metabolite was 659 +/- 192 min. The apparent fraction of sulfinpyrazone absorbed was 0.93 +/- 0.24 and the free fraction in plasma was 1.26 +/- 0.04%. Since the sulfide metabolite has a more potent antiplatelet effect and its formation in normal subjects is variable, direct administration of the sulfide may provide a more predictable antithrombotic effect in patients.

Absorption↗
PubMed1982

Dipyridamol kinetics.

The kinetics of the antiplatelet drug dipyridamole were studied in six normal subjects (three men and three women) who were ages 22 to 34 yr old. Each received 20 mg IV and four also took a 50-mg oral dose. Blood samples were collected after each dose for a period of 3 days and concentrations of dipyridamole were measured by a sensitive and specific high-performance liquid chromatographic assay. Concentrations after the intravenous dose showed a triexponential decline with a terminal half-life of 11.6 +/- 2.2 hr (x +/- SD). Total plasma clearance was 8.27 +/- 1.82 1/hr and the apparent volume of distribution was 141 +/- 51 1. Concentrations rose 6 to 10 hr after intravenous dipyridamole in each female subject, but not in the male subjects. Dipyridamole blood/plasma concentration ratio changed from an average of 0.7 over the first hour to 1.2 after 5 hr after the intravenous dose. There was an absorption lag time ranging from 34 to 75 min after the oral dose; concentrations peaked at about 2 to 2.5 hr after the dose. The percentage of unbound drag in plasma was 0.88 +/- 0.24%. Systemic availability of the end oral dose was 43 +/- 13%. These results suggest widely varying concentrations in patients receiving the drug, and raise questions about the current clinical practice of using empirical dosage schedules.

Administration, Oral↗
PubMed1977

Species variation in pancreatic islet monoamine uptake and action.

There are conflicting data in the literature regarding the role of monamines in the secretion of insulin. In order to clarify the contribution that species variation may make to these divergent results, the uptake of serotinin (5-HT), dopamine (DA), and their precursor amino acids, 5-hydroxytryptophan (5-HTP) and L-dopa, into islets was studied. Islets from golden hamsters, rabbits, guinea pigs, and obese, hyperglycemic mice were isolated by the collagenase technique. The islets were incubated in Krebs-Ringer buffer in the presence of 14C-labeled monamines or their precursors. At 30-minute intervals after initiating the study, the incubation mixture was passed through a Millipore filter. The retained islets were disrupted by sonication and the radioactivity counted. The ratio of the uptake of 5-HTP to 5-HT was at least 3:1 in the hamster, guinea pig, and mouse. In the rabbit the ratio was 1:1. A similar relationship was noted for the uptake of L-dopa and DA. The in-vitro results were confirmed by the in-vivo studies, in which hamsters were injected with 14C5-HT or 5-HTP, followed by isolation of the islets. We conclude that there is significant species variation inthe uptake of these monoamines and their precursors.

5-Hydroxytryptophan↗